The Secret Life of Hormones: Rosalyn Yalow and the Discovery of Radioimmunoassaying

There’s an unsung immensity in the craft of Measuring Things Better. Within our twisting cleverness for developing better and better measurement tools there lies the secret of our advancement not only as science-doers, but as a species generally. The dramatic potential for improving human life through better measurement has no grander success story than that of Rosalyn Yalow, co-discoverer of Radioimmunoassaying (RIA), the technique that not only solved the mystery of what Type II Diabetes is all about, but also more or less invented the field of modern Endocrinology.

Throughout the 1950s, Yalow worked with the several shades too brilliant Solomon Berson in developing new methods to measure first the flow of blood, and then the flow of substances within the blood, using newly available radioactive isotopes as markers. It was a new approach to a problem that had been previously studied by cutting major arteries of condemned criminals, and catching the blood in a graduated bucket. Knife, Stopwatch, Science.

It was not terribly accurate and, sad to say, it was not an isolated case of the American medical establishment using criminals for non-consensual testing prior to, and even well after, the Second World War. The work that Yalow did on blood flow and on the products of the thyroid gland (which also didn’t take heed of the notion of Medical Consent, we should note, though she did everything she could to minimize the danger to the subject) gave her, a nuclear physicist by education, the practical training in preparing and measuring radioactive isotopes for what would become the great discovery of her life.

For there was a terrible mystery at the time surrounding Type II Diabetes. Whereas Type I was relatively well understood as resulting from an insufficiency of insulin in the blood, and could therefore be treated by regular injection of pig insulin, Type II was a bit baffling. Those suffering seemed to be producing insulin just fine, and yet still had the issues with blood sugar maintenance of those suffering from Type I. To get to the bottom of the mystery, somebody had to find a way to measure the amount of insulin in the blood at different times.

This was, to put it mildly, difficult. Insulin exists in miniscule quantities in the blood, far too dilute for any technique of the time to detect. So, Yalow and Berson developed a deliciously simple hack that formed the basis for an entire industry or twelve. They discovered that, when they injected insulin that had been radioactively tagged into the body of a person who had been receiving insulin injections, those tagged insulin molecules were latched onto by globulin molecules which they soon realized were antibodies produced by the host.

That was controversial enough. Insulin is, relatively speaking, a small molecule, and the medical wisdom of the day said that only massive molecules could trigger antibody responses. In their landmark paper of 1956, Yalow and Berson even had to remove the word “antibody” from their prospective title or face rejection of the whole article. But while the scientific community might have been huffing about the name, Yalow and Berson pushed on with a critical insight.

They saw that a patient’s native insulin, when present, also occupied space on these antibodies and therefore knew that, if you took a sample of patient blood, mixed it with antibodies and radioactively tagged insulin, you could tell how much insulin was in the blood by measuring the ratio of radioactive insulin molecules wrapped up by an antibody to those left alone in solution. The more radioactive isotope in solution, the more native insulin there must be.

So, as long as any substance has a corresponding binding molecule, be it an antibody or something similar (as in the case with the B12 assaying later done in the Yalow-Berson lab), you can use RIA to measure the concentration of that substance by producing a radioactive copy, and setting it into competition with its natural counterpart for space on the binding molecule. As the common metaphor runs, it’s hormonal musical chairs. Measure the radioactive kids left standing on their own, chairless, and you have at last a measure of how many “normal” kids there must be, seated but invisible.

Yalow and Berson refused to patent their methods, believing them too important to the future of medicine to be owned by anybody. And so, people around the world flew to reproduce the success of Yalow’s insulin experiments with other hitherto unmeasurable hormones and peptides. The great blank book of the endocrine system unfolded itself under RIA methods, and after Berson died, Yalow deepened the search to the brain, finding there peptides that served as neurotransmitters, of all things, and therefore giving us a whole new perspective on the major players of neurochemistry. By finding a new way of measuring incredibly dilute and relatively lightweight solutes, Yalow gifted humanity all of the improvements in the treatment of disease that have come from the expansion of our hormonal and neurochemical arsenal.

All well and good, but where is the brisk summary of her life, the anecdotes of her growing years, the personal moments of emotional depth? They’re not here, and won’t be. Rosalyn Yalow, unique among the scientists we’ve looked at so far, IS her work. A headstrong daughter of Depression-era Jewish immigrant stock dubbed The Queen Bee by her family, she knew exactly what she wanted from an early age – a life devoted to science, and a family who recognized the primacy that science had in her life and didn’t question her decisions.

Through unadulterated force of will, she attained both. Her husband, Aaron Yalow, a physicist himself and ultra-Orthodox Jew, worshipped her and made a deal with her that, as long as she kept a kosher household, he would give her free rein in all other areas of life. Her children understood that, in matters of sentiment or humor or vulnerability, they were to look to their father, as their mother simply didn’t have those qualities and didn’t care to have them. She didn’t form deep relationships with other women, had no side interests or hobbies, never told jokes, and spent every available moment in her lab with Sol Berson. She was on a mission to show that a woman could have a family and still do top quality research, and in her need to appear perfect, had a tendency to discount the troubles of those close to her. The roll call of her life features a steady stream of awards and honors after her and Berson’s landmark 1956 paper, culminating in the 1977 Nobel Prize, and an impressive array of discoveries well into her sixties, but few moments of purely personal connection with other humans.

One would like to think that this was simply her way, that she didn’t feel the lack of human warmth because she wasn’t interested in it, that her mind and heart were completely satisfied by her work and her reputation as a perfect human who raised an immaculate family with one hand while solving the world’s endocrinology problems with the other. The darker possibility, that she felt the loss but tucked it deep away, knowing that any sign of weakness would hurt the chances of later women pursuing a career in medicine, that she sacrificed herself tirelessly for the greater cause of expanding opportunity, is testified to by the deep but quickly sublimated loss she felt upon the early death of Berson in 1972, and her lifelong drive to make sure that his name was mentioned with hers any time their work in RIA was mentioned.

Yalow officially retired at age 70, in 1991, but continued keeping an office at the Bronx VA even after the effects of strokes and a broken hip had rendered her all but immobile, accepting invitations to speak about the future of women in science, the importance of nuclear research, and the need for more public medical funding. Her work was done in that grand spirit of public medicine that was swallowed whole with the development of pharmaceutical monopolies in the Sixties and Seventies, a time when young researchers still had options outside of industry for making a steady and honorable living, a time that Yalow brought alluringly to life each time she spoke of the glory days, working on a shoestring budget in a makeshift lab with Solomon Berson to understand the hidden world of hormone regulation.

Rosalyn Sussman Yalow died in 2011 in The Bronx.

FURTHER READING: Eugene Straus’s Rosalyn Yalow: Nobel Laureate. Her Life and Work in Medicine is a great source from somebody who worked closely with her for a long stretch of time, and observed astutely her relationship with her children and colleagues. It treats us to long personal reflections from both of her children, and a deeply sad account of how, at the age of 75, she was dumped at a hospital after a severe stroke. The chronology hops around a bit, which is narratively interesting but makes it a bit difficult to nail down the relative sequence of events in her life, but the scientific explanations are clearly and elegantly stated.